No / This review aims to disentangle cause and effect in the relationship between anisometropia and amblyopia. Specifically, we examine the literature for evidence to support different possible developmental sequences that could ultimately lead to the presentation of both conditions. The prevalence of anisometropia is around 20% for an inter-ocular difference of 0.5D or greater in spherical equivalent refraction, falling to 2-3%, for an inter-ocular difference of 3D or above. Anisometropia prevalence is relatively high in the weeks following birth, in the teenage years coinciding with the onset of myopia and, most notably, in older adults starting after the onset of presbyopia. It has about one-third the prevalence of bilateral refractive errors of the same magnitude. Importantly, the prevalence of anisometropia is higher in highly ametropic groups, suggesting that emmetropization failures underlying ametropia and anisometropia may be similar. Amblyopia is present in 1-3% of humans and around one-half to two-thirds of amblyopes have anisometropia either alone or in combination with strabismus. The frequent co-existence of amblyopia and anisometropia at a child's first clinical examination promotes the belief that the anisometropia has caused the amblyopia, as has been demonstrated in animal models of the condition. In reviewing the human and monkey literature however it is clear that there are additional paths beyond this classic hypothesis to the co-occurrence of anisometropia and amblyopia. For example, after the emergence of amblyopia secondary to either deprivation or strabismus, anisometropia often follows. In cases of anisometropia with no apparent deprivation or strabismus, questions remain about the failure of the emmetropization mechanism that routinely eliminates infantile anisometropia. Also, the chronology of amblyopia development is poorly documented in cases of 'pure' anisometropic amblyopia. Although indirect, the therapeutic impact of refractive correction on anisometropic amblyopia provides strong support for the hypothesis that the anisometropia caused the amblyopia. Direct evidence for the aetiology of anisometropic amblyopia will require longitudinal tracking of at-risk infants, which poses numerous methodological and ethical challenges. However, if we are to prevent this condition, we must understand the factors that cause it to develop.

Yes / The NHS spends billions of pounds annually on repeat prescriptions in primary care, but data on their extent and use is out of date. Understanding the scale of repeat prescribing and for whom it is prescribed is important for the NHS to plan services and develop policies to improve patient care. Anonymous data on prescription numbers and practice population demographics was obtained from GP computer systems in a large urban area.Searches were conducted in November 2011 to identify the numbers of repeat items listed on individuals' repeat lists by sex and age.The proportion of all prescription items issued as repeats was identified by conducting searches on items issued as repeat and acute prescriptions. In the year of study 4,453,225 items were issued of which 3,444,769 (77%) were repeats (mean 13 items per patient/annum) and 1,008,456 (23%) acute prescriptions (mean 3.9 items per patient per annum). The mean number of repeat Items per patient was 1.87 (range 0.45 ages 0-9 years; 7.1 ages 80-89 years). At least one repeat medicine was prescribed to 43% of the population (range 20% for ages 0-9; over 75% for ages 60+). A significant proportion of the population receive repeat prescriptions and the proportion increases with age. Whilst the proportion of repeat items to acute items has remained unchanged over the last two decades the number of repeat prescriptions items issued has doubled (from 5.8 to 13.3 items/patient/annum). This has implications for general practice workload, patient convenience, NHS costs and risk.

Wu Man Sze Anise. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 72-84). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.ii / ABSTRACT --- p.iii / TABLE OF CONTENTS --- p.vi / LIST OF TABLES --- p.viii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Health Habits --- p.2 / Health Habits and Health Status of Elderly Adults --- p.2 / Health Habits among Chinese Elders with Diabetes --- p.3 / Measurement of Health Habits --- p.5 / Perceived Control --- p.6 / Perceived Control over Health --- p.6 / Health Locus of Control and Health Value --- p.7 / Self-efficacy --- p.15 / Previous Research Focus of Effect of Perceived Control on Chronic Illness --- p.16 / Perceived Control and Chinese Culture --- p.19 / Chapter CHAPTER 2 --- MAIN STUDY --- p.20 / Purpose of the Present Study --- p.20 / Method --- p.22 / Participants --- p.22 / Instruments --- p.24 / Health Habits --- p.24 / Health Locus of Control --- p.25 / Health Value --- p.26 / Self-efficacy --- p.26 / Health Status --- p.26 / Blood Glucose Control --- p.27 / Demographics --- p.27 / Procedure --- p.28 / Data Analysis --- p.28 / Results --- p.30 / Results for the First Wave Data --- p.30 / Analysis of Demographic Information --- p.30 / Analyses of Blood Glucose --- p.33 / Factor Analyses of Health Habits --- p.35 / Analysis of Demographic/ Medical Effects on Two Health Habits Dimensions --- p.36 / Correlations among Psychological Variables and Health Habits at Time1 --- p.38 / Regression Analyses of General Health Habits at Time1 --- p.40 / Regression Analyses of Diabetes-related and Preventive Health Habits at Time1 --- p.42 / Results for Second Wave Data --- p.45 / Correlations of Health Habits/Health Status at --- p.45 / Time 1 and Health Status at Time2 / Changes across Time --- p.46 / Stepwise Regression Analysis of Health Habits at Time2 --- p.47 / Discussion --- p.50 / Predictors of Health Habits at Time1 --- p.50 / Predictive Power of Psychological Constructs over --- p.57 / Habits at Time2 / Glycemic Control --- p.58 / Demographic and Medical Influences on Health --- p.60 / Status and Psychological Variables / Limitations --- p.61 / Research and Practical Implications --- p.63 / Conclusion / REFERENCES --- p.70 / FOOTNOTES --- p.72 / APPENDIX A Health Habits Checklist --- p.85 / APPENDIX B Self-efficacy (Toward Health Habits) and Health Value Scales --- p.103 / APPENDIX C Multidimensional Health Locus of Control Scales --- p.104

Text in Afrikaans / Hierdie navorsing handel oor ouderdom en geslag as veranderlikes in die salutogenese paradigma. Die salutogenese paradigma het sy ontstaan en ontwikkeling aan verskeie navorsingsperspektiewe te danke. Daar is reeds op internasionale gebied breedvoerig navorsing oor hierdie paradigma gedoen. In die Suid-Afrika is die navorsing van Strumpfer en Wissing goed bekend. In hierdie navorsing is daar deur middel van faktorontleding gepoog om die onderliggende dimensies van die konstrukte gevoel van koherensie en geharde persoonlikheid bloot te le. Daar is onderskeidelik twee duidelike faktore vir beide konstrukte bepaal. Die faktore op die Lewensorientasievraelys (OLQ) het noue ooreenstemming getoon met die komponente betekenisvolheid en hanteerbaarheid (OLQ1 ), en verstaanbaarheid (OLQ2) soos deur Antonovsky (1987) bespreek. Die faktore op die "Personal Views Survey" (PVS) het ooreenstemming getoon met die komponente verbintenis en beheer (PVS1) en uitdaging (PVS2), soos deur Kobasa (1979) daargestel. Hierdie navorsingsresultate toon verder dat ouderdom wel die mate van gevoel van koherensie wat 'n individu mag ervaar, kan be"invloed. Alhoewel geslag in 'n mindere mate 'n invloed op die mate van gevoel van koherensie getoon het, behoort geslag (in perspektief van die totale steekproef beskou) nie 'n bepalende invloed uit te oefen nie. In terme van die mate van geharde persoonlikheid wat 'n individu mag ervaar, het ouderdom en geslag geen invloed getoon nie. Daar is ook geen interaksie-effek tussen ouderdom en geslag en die onderskeie konstrukte vasgestel nie. / This research project deals with age and gender as variables in the salutogenesis paradigm. The salutogenesis paradigm owes its origin and development to various research projects. Research in the international field has already been done on this paradigm on a wide sphere. The research of Strumpfer and Wissing is well known in South Africa. In this area of research an attempt is made through the analysis of factors to expose the underlying dimensions of the construct sense of coherence and the construct hardy personality. Two certain factors for both constructs have been indicated. The factors influencing the Orientation to Life Questionnaire indicated a close resemblance with the components of meaningfulness and manageability (OLQ1), and comprehensibility (OLQ2), discussed by Antonovsky (1987). The factors of the Personal Views Survey (PVS) demonstrated a similarity with the components commitment and control (PVS 1) and challenge (PVS2), as stated by Kobasa (1979). The results of this research demonstrates that age may well influence the measure of the sense of coherence which an individual may experience. Although gender indicated a minor measure of influence on the degree of sense of coherence, gender should not (in perspective of this research findings) have a deciding influence. Age and gender indicated no deciding influence in the measure of hardy personality experienced by an individual. Age and gender did not manifest any interaction in the various constructs. / Industrial and Organisational Psychology / M. Com. (Bedryfsielkunde)

<p>Увод: Пинеална жлезда је неуроендокрини, циркумвентрикуларни орган филогенетски пореклом органа вида. Калцификације пинеалне жлезде су чест налаз приликом радиолошких претрага, без још увек довољно доказа да ли су оне нормалан налаз. Магнетна резонанца описује три морфолошка типа пинеалне жлезде. Циљеви: Утврдити степен корелације морфолошких типова пинеалне жлезде утврђених патохистолошким налазом са налазом компјутеризоване томографије, као и степен корелације присуства калцификација у пинеалној жлезди утврђених патохистолошким налазом и налазом компјутеризоване томографије. Утврдити степен калцификације пинеалне жлезде патохистолошким налазом у зависности од старости. Материјал и методе: Макроскопском морфолошком и микроскопском, хистолошком анализом обухваћено је 111 изолованих пинеалних жлезди осoба оба пола, не млађих од 18 година од којих је 27 снимљено апаратом Somatom Sensation 64 са дебљинама реконструисаних пресека 5 и 1mm, а још 9 апаратом Somatom Emotion 16. Резултати: Постоји статистички значајна разлика у одређивању сва три дијаметра епифизе петомилиметарским реконструкцијама, и при утврђивању два дијаметра једномилиметарским реконструкцијама. Постоји статистички значајна разлика у утврђивању морфолошких типова хистолошком и методом компјутеризоване томографије. Присутна је позитивна корелација калцификованости жлезде одређене мерењем њене густине у Хаунсфилдовим јединицама и утврђене микроскопски. Калцификованост пинеалног паренхима не корелира старости. Закључак: Наша студија је показала да су једномилиметарске реконструкције тачније у одређивању дијаметара жлезде. Макроскопским и микроскопским мерењем утврђена су сва три типа пинеалне жлезде описана магнетнорезонантним осликавањем. Утврђена је статистички значајна повезаност густине пинеалне жлезде измерене у Хаунсфилдовим јединицама на једномилиметарским реконструкцијама и степена калцификованости израженог у процентима. Није утврђена повезаност калцификованости епифизе мерене микроскопски и старости.</p> / <p>Uvod: Pinealna žlezda je neuroendokrini, cirkumventrikularni organ filogenetski poreklom organa vida. Kalcifikacije pinealne žlezde su čest nalaz prilikom radioloških pretraga, bez još uvek dovoljno dokaza da li su one normalan nalaz. Magnetna rezonanca opisuje tri morfološka tipa pinealne žlezde. Ciljevi: Utvrditi stepen korelacije morfoloških tipova pinealne žlezde utvrđenih patohistološkim nalazom sa nalazom kompjuterizovane tomografije, kao i stepen korelacije prisustva kalcifikacija u pinealnoj žlezdi utvrđenih patohistološkim nalazom i nalazom kompjuterizovane tomografije. Utvrditi stepen kalcifikacije pinealne žlezde patohistološkim nalazom u zavisnosti od starosti. Materijal i metode: Makroskopskom morfološkom i mikroskopskom, histološkom analizom obuhvaćeno je 111 izolovanih pinealnih žlezdi osoba oba pola, ne mlađih od 18 godina od kojih je 27 snimljeno aparatom Somatom Sensation 64 sa debljinama rekonstruisanih preseka 5 i 1mm, a još 9 aparatom Somatom Emotion 16. Rezultati: Postoji statistički značajna razlika u određivanju sva tri dijametra epifize petomilimetarskim rekonstrukcijama, i pri utvrđivanju dva dijametra jednomilimetarskim rekonstrukcijama. Postoji statistički značajna razlika u utvrđivanju morfoloških tipova histološkom i metodom kompjuterizovane tomografije. Prisutna je pozitivna korelacija kalcifikovanosti žlezde određene merenjem njene gustine u Haunsfildovim jedinicama i utvrđene mikroskopski. Kalcifikovanost pinealnog parenhima ne korelira starosti. Zaključak: Naša studija je pokazala da su jednomilimetarske rekonstrukcije tačnije u određivanju dijametara žlezde. Makroskopskim i mikroskopskim merenjem utvrđena su sva tri tipa pinealne žlezde opisana magnetnorezonantnim oslikavanjem. Utvrđena je statistički značajna povezanost gustine pinealne žlezde izmerene u Haunsfildovim jedinicama na jednomilimetarskim rekonstrukcijama i stepena kalcifikovanosti izraženog u procentima. Nije utvrđena povezanost kalcifikovanosti epifize merene mikroskopski i starosti.</p> / <p>Introduction: Pineal gland is a small neuroendocrine, circumventricular organ wich evolved from the eye. Calcifications were incidentally discovered and frequently without a proof whether they were normal or abnormal. Magnetic resonance imaging describes three morphological types. Aim: To determine if there is a correlation between pineal gland morphology types and calcifications established with histology and with computed tomography (CT) and if there is the correlation between calcifications and age. Method of work and material: Macroscopic and mycroscopic analysis encounted 111 isolated pineal glands of both sexes, no younger than 18, from wich 27 was examed with Somatom Sensation 64 and 9 with Somatom Emotion 16 with 5mm and 1mm reformated pictures. Results: All three diameters measured on 5mm reformated pictures and two measured on 1mm reformated pictures differed statistically compared to diameters measured macroscopically. There was siginificant difference between morphological types established on computed tomography and macroscopically. Pineal gland calcifications measured microscopically and with CT correlated positivelly. Pineal gland calcifications were not dependant on the patients age. Conclusion: Allthough 1mm reformated pictures are more accurate than 5mm, the pineal gland morpholgy types determined macroscopically and with CT are not correlated. However, calcification measurement with CT correlates with the microscopic measurement. Calcifications measured microscopically are not correlated with age.</p>

Research into the reminiscence bump aims to improve our understanding of how the memories formed during our adolescence and early adulthood subsequently influence our autobiographical recollections later in life. The purpose of this study was to investigate the temporal dynamics of autobiographical memory in a sample involving two different age groups of adult South African participants. The main objective of the research was to explore the participants’ memories for salient events and to determine whether these memories exhibit the typical reminiscence bump that has been found in autobiographical memory research. This sample consisted of two sets of cohorts, totalling 48 research participants. The first group comprised participants ranging between the ages of 40 and 59 years, and the second group involved participants ranging between the ages of 60 to 79 years. A convergent parallel mixed method approach was adopted in this study. Both quantitative and qualitative data, on the distribution, valence and life domain importance of the reminiscence bump, were collected through the lifeline interview method. The results confirmed that reminiscence bumps are reflected in the memories of both age groups between the ages of 10 and 30 years. Most life events recalled were of positive affect thus confirming the positivity bias in older adults. The family and home life domains were indicated as the most important life domains in the autobiographical memories of both groups. The main conclusion drawn from the study was that there was not a significant difference in the dynamics of the autobiographical memories between the two groups, as reflected in the temporal characteristics of their reminiscence bumps. Future research could further explore the patterns of memories, and researchers could in particular investigate the semantic and affective aspects of these autobiographical memories in more depth. / Psychology / M.A. (Psychology)

The neurophysiological basis of cognition changes with age is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event related potentials, brain size and cerebral blood flow. Proton magnetic resonance spectroscopy (1H-MRS) is an in vivo method used to detect metabolites within the brain that are relevant to certain brain processes. Recent studies have shown that these metabolites, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in patients with a variety of cognitive disorders associated with ageing and in normal ageing subjects. We have studied the relationship between metabolites and cognitive function in elderly patients 3 months and 3 years after a stroke or transient ischemic attack (TIA) and in an ageing comparison group. Metabolites were no different between stroke/TIA patients and elderly controls, however, there were significant metabolite differences between stroke/TIA patients with cognitive impairment (Vascular Cognitive Impairment and Vascular Dementia) and those without. Frontal measures of NAA and NAA/Cr predicted cognitive decline over 12 months and 3 years in stroke/TIA patients and elderly controls, and these measures were superior predictors than structural MRI measures. Longitudinal stability of metabolites in ageing over 3 years was associated with stability of cognitive function. The results indicate that 1H-MRS is a useful tool in differentiating stroke/TIA patients with and without cognitive impairment, with possibly superior predictive ability than structural MRI for assessing future cognitive decline. The changes in 1H-MRS that occur with ageing and cognitive decline have implications for the neurophysiological mechanisms and processes that are occurring in the brain, as well as application to clinical diagnosis, the early detection of pathology and the examination of longitudinal change.

The point of concentration for this study was to estimate the extent to which health-promoting habits might predict medication-compliant practices among older adults. The purpose was to recognize potentially non-adhering persons, identify attitudes leading to healthy habits, and signal any practices contributing to non-compliant behaviors. Selected were patients who ranged in age from minimum 62, lived independently, self-administered medication regimes, had a chronic ailment that had persisted for at least 12 months, and regularly attended a geriatric clinic sited in the midwestern United States. A non-probability convenience sample (n = 100) was analyzed by a descriptive correlational approach to test self-proclaimed relations between health habits and compliant practices. The instrument used to measure health habits that would enrich life was the Health-Promoting Lifestyle Profile II created and promoted by Walker, Sechrist, and Pender (1995). The tool used to decide levels of medication adherence was a compliance profile created specifically for this study. Demographic information was collected for age, race, marital status, gender, and education. Descriptive statistics were calculated for each variable and Pearson product-moment correlation coefficient was utilized to decide what, if any, real and measurable interrelationships exist between the health-promoting habits and medication-compliant practices among an older population. The t-test was utilized in determining differences in both healthpromoting lifestyle habits and medication-compliant practices between older males and females. The significance level used to evaluate every theory was p < .05. Discovery gave no statistically critical relationship between overall health-promoting lifestyle habits and medication-compliant practices among the constituents of an older populace. Findings gave no significant variance between men and women in either lifestyle habits or compliance practices as a whole, but the HPLP II categories of Interpersonal Relations and Nutrition did mirror a significant difference between genders. / Department of Physiology and Health Science

"A thesis submitted in partial fulfillment of the requirements for the award of the degree of Doctor of Philosophy". / Thesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007. / Bibliography: p. 243-277. / Introduction -- A convenient synthesis of 30HKG -- Facile synthesis of the UV filter compounds 30HKyn and AHBG -- Synthesis, identification and quantification of novel human lens metabolites -- Modification of bovine lens protein with UV filters and related metabolites -- Effect of UV light on UV filter-treated lens proteins -- Conclusions and future directions. / The kynurenine-based UV filters are unstable under physiological conditions and undergo side chain deamination, resulting in α,β-unsaturated carbonyl compounds. These compounds can react with free or protein bound nucleophiles in the lens via Michael addition. The key sites of the UV filters kynurenine (Kyn) and 3-hydroxykynurenine (3OHKyn) modification in human lenses include cysteine (Cys), and to a lesser extent, lysine (Lys) and histidine (His) residues. Recent in vivo studies have revealed that 3-hydroxykynurenine-O-β-D-glucoside (3OHKG) binds to Cys residues of lens crystallins in older normal human lenses. As a result of this binding, human lens proteins become progressively modified by UV filters in an age-dependent manner, contributing to changes that occur with the development of age-related nuclear (ARN) cataract. Upon exposure to UV light, free UV filters are poor photosensitisers, however the role of protein-bound species is less clear. It has been recently demonstrated that Kyn, when bound to lens proteins, becomes more susceptible to photo-oxidation by UV light. Therefore, the investigation of 3OHKG binding to lens proteins, and the effect of UV light on proteins modified with 3OHKG and 3OHKyn, were major aims of this study. As a result of the role of these compounds as UV filters and their possible involvement in ARN cataract formation, it is crucial to understand the nature, concentration and modes of action of the UV filters and their metabolites present in the human lenses. Therefore, an additional aim was to investigate human lenses for the presence of novel kynurenine-based human lens metabolites and examine their reactivity.--As 3OHKG is not commercially available, to conduct protein binding studies, an initial aim of this study was to synthesise 3OHKG (Chapter 2). Through the expansion and optimisation of a literature procedure, 3OHKG was successfully synthesised using commercially available and inexpensive reagents, and applying green chemistry principles, where toxic and corrosive reagents were replaced with benign reagents and solvent-free and microwave chemistry was used. A detailed investigation of different reaction conditions was also conducted, resulting in either the improvement of reaction yields or reaction time compared to the literature method. Applying the same synthetic strategy, and using key precursors from the synthesis of 3OHKG, the UV filters 3OHKyn and 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid-O-β-D-glucoside (AHBG), were also successfully synthesised (Chapter 3). / Chapter 4 describes the investigation of both normal and cataractous human lenses in an attempt to identify novel human lens metabolites derived from deaminated Kyn and 3OHKyn (Chapter 4, Part A). Initially, 4-(2-aminophenyl)-4-oxobutanoic acid (AHA), glutathionyl-kynurenine (GSH-Kyn), kynurenine yellow (Kyn yellow), 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid (AHB), glutathionyl-3-hydroxykynurenine (GSH-3OHKyn) and 3-hydroxykynurenine yellow (3OHKyn yellow) were synthesised and human lenses were examined for their presence. AHA and AHB were synthesised from similar precursors to those used in the synthesis of 3OHKG, while the GSH adducts and yellow compounds were synthesised from Kyn and 3OHKyn via base induced deamination. Following isolation and structural elucidation, AHA, AHB and GSH-Kyn were confirmed as novel human lens metabolites. They were quantified in low pmol/mg lens (dry mass) levels in normal and cataractous lenses of all ages, while GSH-3OHKyn, Kyn yellow and 3OHKyn yellow were not detected. In contrast to AHA, the lens metabolites AHB, GSH-Kyn and GSH-3OHKyn were found to be unstable at physiological pH. The spectral properties of these compounds suggest that they may act as UV filters. --Chapter 4 (Part B) also describes the identification and characterisation of a novel human lens UV filter, cysteinyl-3-hydroxykynurenine -O-β-D-glucoside (Cys-3OHKG). An authentic standard was synthesised via Michael addition of cysteine to deaminated 3OHKG. Cys-3OHKG was detected in low pmol/mg lens (dry mass) levels in normal lenses only after the 5th decade of life and was absent in cataractous lenses. Cys-3OHKG showed rapid decomposition at physiological pH. / Chapter 5 describes the identification and quantification of amino acids involved in covalent binding of 3OHKG to lens proteins. Model studies with bovine lens proteins and 3OHKG at pH 7.2 and 9.5 were undertaken. The amino acid adducts were identified via total synthesis and spectral analysis, and subsequently quantified upon acid hydrolysis of the modified lens proteins. Under both pH conditions, 3OHKG was found to react with lens proteins predominantly via Cys residues with low levels of binding also detected at Lys residues. Comparative studies with Kyn (pH 9.5) and 3OHKyn (pH 7.2 and 9.5) resulted in modified lens proteins at Cys residues, with only minor modification at Lys residues at pH 9.5. The extent of modification was found to be significantly higher at pH 9.5 in all cases. His adducts were not identified. 3OHKG-, Kyn- and 3OHKyn-modified lens proteins were found to be coloured and fluorescent, resembling those of aged and ARN cataractous lenses. In contrast, AHB and AHA, which can not form α,β-unsaturated carbonyl compounds, resulted in non-covalent modification of lens proteins. AHB may contribute to lens colouration and fluorescence as further reactions of this material yielded species that have similar characteristics to those identified from 3OHKyn modification. These species are postulated to arise via auto-oxidation of the o-aminophenol moiety present in both 3OHKyn and AHB.--In Chapter 6, the potential roles of 3OHKG and 3OHKyn, and the related species AHA and AHB, in generating reactive oxygen species and protein damage following illumination with UV light was examined. The UV filter compounds were examined in both their free and protein-bound forms. Kyn-modified proteins were used as a positive control. Exposure of these compounds to UV light (λ 305-385 nm) has been shown to generate H2O2 and protein-bound peroxides in a time-dependent manner, with shorter wavelengths generating more peroxides. The yields of peroxides were observed to be highly dependent on the nature of the UV filter compound and whether these species were free or protein bound, with much higher levels being detected with the bound species. Thus, protein-bound 3OHKyn yielded higher levels of peroxide than 3OHKG, with these levels, in turn, higher than for the free UV filter compounds. AHB-treated lens proteins resulted in formation of low but statistically significant levels of peroxides, while AHA-treated lens proteins resulted in insignificant peroxide formation. The consequences of these photochemical reactions have been examined by quantifying protein-bound tyrosine oxidation products (3,4-dihydroxyphenylalanine [DOPA], di-tyrosine [di-Tyr]) and protein cross-linking. 3OHKG-modified proteins gave elevated levels of di-Tyr, but not DOPA, whereas 3OHKyn-modified protein gave the inverse. DOPA formation was observed to be independent of illumination and most likely arose via o-aminophenol auto-oxidation. AHB- and AHA-treated lens proteins resulted in statistically insignificant di-Tyr formation, while a light independent increase in DOPA was observed for both samples. Both reducible (disulfide) and non-reducible cross-links were detected in modified proteins following illumination. These linkages were present at lower levels in modified, but non-illuminated proteins, and absent from unmodified protein samples. / This work has provided an optimised synthetic procedure for 3OHKG and other lens metabolites (Chapters 2 and 3). Four novel lens metabolites have been identified and quantified in normal and cataractous human lenses (Chapter 4). Subsequent experiments, described in Chapter 5, identified the major covalent binding sites of 3OHKG to lens proteins, while AHA and AHB showed non-covalent binding. Further work described in Chapter 6 showed that protein-bound 3OHKG, Kyn and 3OHKyn were better photosensitisers of oxidative damage than in their unbound state. Together, this research has provided strong evidence that post-translational modifications of lens proteins by kynurenine-based metabolites and their interaction with UV light appear, at least in part, responsible for the age-dependent colouration of human lenses and an elevated level of oxidative stress in older lenses. These processes may contribute to the progression of ARN cataract. / Mode of access: World Wide Web. / xxxix, 308 p. ill. (some col.)

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.